Randomized Controlled Trial

. 2024 Jun 3;21(6):e1004375.

doi: 10.1371/journal.pmed.1004375. eCollection 2024 Jun.

Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules

Amanda Jane Leach¹, Nicole Wilson¹, Beth Arrowsmith^{1

2}, Jemima Beissbarth¹, Kim Mulholland^{3

4

5}, Mathuram Santosham^{6

7}, Paul John Torzillo^{8

9}, Peter McIntyre^{10

11}, Heidi Smith-Vaughan¹, Sue A Skull¹², Victor M Oguoma^{1

13}, Mark D Chatfield^{1

14}, Deborah Lehmann², Christopher G Brennan-Jones^{2

15}, Michael J Binks^{1

16}, Paul V Licciardi^{3

4}, Ross M Andrews¹⁷, Tom Snelling¹⁸, Vicki Krause¹⁹, Jonathan Carapetis^{2

12}, Anne B Chang^{1

20}, Peter Stanley Morris^{1

21}

Affiliations

¹ Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
² Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
³ London School of Hygiene and Tropical Medicine, London, United Kingdom.
⁴ Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
⁶ Departments of International Health and Pediatrics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
⁷ Center for Indigenous Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
⁸ Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
⁹ Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
¹⁰ Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
¹² Division of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
¹³ Poche Centre for Indigenous Health, The University of Queensland, Brisbane, Queensland, Australia.
¹⁴ Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
¹⁵ School of Allied Health, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.
¹⁶ Women and Kids Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
¹⁷ Office of the Chief Health Officer, Queensland Health, Brisbane, Queensland, Australia.
¹⁸ School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
¹⁹ Centre for Disease Control (CDC)-Environmental Health, Northern Territory Health, Darwin, Northern Territory, Australia.
²⁰ Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
²¹ Paediatrics Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia.

PMID: 38829821
PMCID: PMC11146696
DOI: 10.1371/journal.pmed.1004375

Randomized Controlled Trial

Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules

Amanda Jane Leach et al. PLoS Med. 2024.

. 2024 Jun 3;21(6):e1004375.

doi: 10.1371/journal.pmed.1004375. eCollection 2024 Jun.

Authors

Affiliations

¹ Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
² Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
³ London School of Hygiene and Tropical Medicine, London, United Kingdom.
⁴ Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
⁶ Departments of International Health and Pediatrics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
⁷ Center for Indigenous Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
⁸ Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
⁹ Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
¹⁰ Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
¹² Division of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
¹³ Poche Centre for Indigenous Health, The University of Queensland, Brisbane, Queensland, Australia.
¹⁴ Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
¹⁵ School of Allied Health, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.
¹⁶ Women and Kids Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
¹⁷ Office of the Chief Health Officer, Queensland Health, Brisbane, Queensland, Australia.
¹⁸ School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
¹⁹ Centre for Disease Control (CDC)-Environmental Health, Northern Territory Health, Darwin, Northern Territory, Australia.
²⁰ Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
²¹ Paediatrics Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia.

PMID: 38829821
PMCID: PMC11146696
DOI: 10.1371/journal.pmed.1004375

Abstract

Background: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations.

Methods and findings: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size.

Conclusions: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation.

Trial registration: ClinicalTrials.gov NCT01735084 and NCT01174849.

Copyright: © 2024 Leach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Conflict of interest statement

AJL received funds from NHMRC paid to the institution, and GSK provided materials for immunogenicity assays. AJL received funds from Merck Sharp and Dohme for analysis of pneumococcal carriage, payment to institution. ABC served as advisor on a Data Safety Monitoring Board for an unlicensed vaccine (GlaxoSmithKline) and an unlicensed monoclonal antibody (AstraZeneca), was an adviser on an unlicensed molecule for chronic cough (Merck); and has multiple project grants and a Centre of Research Excellence relating to various aspects of bronchiectasis in children from the National Health and Medical Research Council. ABC received Royalties or licences as an author of cough and bronchiectasis topics, and Partial reimbursement for airfares as a speaker for European Respiratory Society. All payments were to the institution. PM served on a data safety and monitoring board for the Novavax COVID-19 vaccine. JB provided a report to Merck Sharp and Dohme Australia. All other authors (DL, CGB-J, HS-V, MJB, MDC, PVL, PSM, PJT) declare no competing interests.

Figures

**Fig 1. Participant flow.**
P: PCV13 13-valent pneumococcal conjugate vaccine. S: PHiD-CV10 10-valent pneumococcal H. *influenzae* protein D conjugate vaccine. *One child allocated to +P received +S.

**Fig 2. Hearing loss prevalence (none, mild, moderate, severe) by booster dose, at ages 12 (baseline), 18 (primary endpoint), 24, 30, and 36 months.**
+P: booster dose of PCV13 13-valent pneumococcal conjugate vaccine. +S: booster dose of PHiD-CV10 10-valent pneumococcal H. *influenzae* protein D conjugate vaccine.

See this image and copyright information in PMC

References

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Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules

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Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules

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